The objective of this research program is to establish the role of interaction between virus defective interfering particles (DIP), infectious standard virus (S-virus) and lymphocytes in the mechanism of virus persistence and dysfunction of the immune system in chronic viral diseases. Results showed that lymphoid tissue of mice acutely or persistently infected with lymphocytic choriemeningitis virus (LCMV) accumulate relatively high amounts of S-virus and DIP. During the persistent infection 0.5-3 percent of the lymphocytes (apparently T cells) are infected with attenuated mutants of LCMV. Regulatory interactions appear to exist between S-virus, its attenuated mutants and DIP. The specific topics of this investigation are: a) persistence of virus in lymphocytes, properties of infected cells as well as of the virus which persists, b) latency of S-virus and DIP in lymphocytes, c) production of DIP in lymphocytes and ability of the latter to support DIP-mediated interference with multiplication of Homologous S-virus d) the effect of infection with S-virus, DIP or DIP plus S-Virus on lymphocyte reactivity.